Table 3.

Impact of probiotics on GI and respiratory immunity in adults.

References	Pop.a	Study design	Probiotic administration	Duration	GI or respiratory symptoms	Biochemistries	Performance outcome
Clancy et al. (57)	17 male & 10 female recreational athletes; 16–40 years	PPI	2 x 1010 CFU/d L. acidophilus LAFTI L10	4weeks	Fatigued athletes present more episodes of URIs/year and lost more activities to illness	Fatigued athletes: increased IFN-gamma production by CD4 cells Non- fatigued athletes: increased salivary IFN-gamma	No performance comparison made between treatment groups.
Moreira et al. (58)	123 male & 16 female trained marathon runners; 39 ± 9 years	DB, PC, RCT, parallel	Milk based L. rhamnosus GG (LGG). 3 x 108 CFU/mL. Participants drank 130 mL/day	3 monthes	No substantial difference in symptoms of atopy or asthma.	No difference between groups	No significant difference in marathon completion time between the treatment groups.
Tiollier et al. (59)	47 trained French Army cadets; 21 ± 0.4 years	DB, PC, RCT, parallel	Milk fermented by L. casei strain DN-114 001	3 weeks + 5 days	No difference between groups on ERTI in incidence.	Prevented the reduction of salivary IgA after training. Immune cells did not differ between groups. DHEA-S increased in probiotics group. Cortisol and prolactin did not change.	No performance comparisons made.
Kekkonen et al. (60)	123 male & 16 female trained marathon runners; 39 ± 9 years	DB, PC, RCT, parallel	Milk based L. rhamnosus GG (LGG). 3 x 108 CFU/mL. Participants drank 130 mL/day	3 months	Decreased number (33%) and duration (57%) of GI symptoms 2 weeks after marathon, but no effects related to URS incidence, compared with placebo	Hematological parameters within reference range for both groups.	No significant difference in marathon completion time between the treatment groups.
Cox et al. (34)	20 elite male runners; 20–34 years	DB, PC	Capsules containing L. fermentum. VRI-003 (PCC) 12 x 109 CFU/d	4 weeks	Reduction in number (50%) of days with respiratory illness symptoms (self-reported)	Modest increase in salivary IgA and IgA1, and IFN-γ. No change in IL-4 and IL-12.	No substantial changes in running performance measures
West et al. (42)	64 male 35 ± 9 years & 35 female 36 ± 9 years elite competitive cyclists	DB, PC, RCT, parallel	One capsule per day containing L. fermentum(PCC) 1 × 109 CFU/d	11 weeks	Increase in mild GI and lower respiratory symptoms compared to placebo.	Reduced perturbations in anti-inflammatory and pro-inflammatory cytokines (IL-1RA, IL-6, IL-8, IL-10, GM-CSF, IFN-γ, TNF-α) in probiotic group.	No difference between groups in performance tests (cycle ergometry, VO2max) or exercise duration.
Martarelli et al. (61)	24 male recreational athletes; 32 ± 6 years	PC, RCT, parallel	Powdered mixtures of the 2 probiotic strains (1:1 L. rhamnosus IMC 501 and Lactobacillus paracasei IMC 502; ~10 × 109 CFU/d)	4 weeks	NR	Increased plasma biological antioxidant potential in probiotic group.	No performance comparisons made between groups.
Gleeson et al. (62)	54 male & 30 female trained endurance athletes; 27 ± 11.6 years	DB, PC, RCT, parallel	Fermented milk containing L. casei Shirota 6.5 x 109 CFU 2 times per day	16 weeks	Placebo group had 36% more URS and higher URTI episodes compared with probiotic group (1.2 vs. 2.1). Severity and duration of symptoms were not significantly different.	Salivary IgA concentration was higher after 8 and 16 weeks compared to placebo. No difference with IgG, IgM, or total immunoglobulin.	No performance comparisons made between groups.
Gleeson et al. (63)	66 trained endurance athletes; 19–28 years	DB, PC, RCT, parallel	Sachets containing L. salivarius*, 2 x 1010 CFU/d	16 weeks	No difference in URS duration between groups, no substantial difference in frequency, duration, or severity or URTI.	No difference in salivary IgA between groups. Probiotic group increased lymphocyte totals, no differences in other blood immune cells.	No performance comparisons made between groups.
Lamprecht et al. (64)	23 male trained athletes; 38 ± 5 years	DB, PC, RCT, parallel	Sachets containing B. bifidum W23 + B. lactis W51 + E. faecium W54 + L. acidophilus W22 + L. brevis W63 + L. lactis W58, 1 × 1010 CFU/d	14 weeks	NR	Reduced TNF concentration (25%) at rest and post-exercise, reduced exercise-induced protein oxidation (8%) compared to placebo. No difference in IL-6 production, or change in total oxidation status of lipids and malondialdehyde.	No performance comparisons made between groups.
Valimaki et al. (65)	125 male & 16 female trained runners; 40 years (22–69)	DB, PC, RCT, parallel	Milk based fruit drink with L. rhamnosus GG 4 × 1010 CFU/d	3 months	NR	Oxidized LDL lipids increased by 28% and 33% during the preparation period and decreased by 16% and 19% during the marathon run in the placebo and probiotic groups, respectively.	No performance comparisons were made.
West et al. (66)	241 male 35 ± 12 years & 224 female 36 ± 12 years trained runners	DB, PC, RCT, parallel	Sachets containing (i) B. animalis subsp. lactis (Bl-04), 2.0 × 109 CFU/d (ii) L. acidophilus NCFM and B. animalis subsp. lactis Bi-07 (NCFM & Bi-07) 5 × 109 CFU/d	164 days	A reduction in URTI episodes in probiotic groups. Symptom severity did not differ between groups.	NR	Significant decrease in activity intensity but increase in activity duration vs placebo.
Haywood et al. (67)	30 male elite rugby players; 20–28 years	PC, RCT, parallel	Capsules probiotics multi-species (L. gasseri*: 2.6 × 1012 CFU/d, B. bifidum*: 0.2 × 1012 CFU/d, and B. longum*: 0.2 × 1012 CFU/d)	4 weeks + 4 weeks washout	Decreased incidence and duration of URTI and GI illness compared to placebo. No difference in symptom severity.	NR	No performance comparisons were made.
Shing et al. (39)	10 male trained runners; 27 ± 2 years	DB, RCT, PC, cross-over	Capsule providing 7.4 x 109 CFU/d of L. acidophilus*, 15.55 x 109 CFU/d of L. rhamnosus*, 9.45 x 109 CFU/day of L. casei*, 3.15 x 109 CFU/d of L. plantarum*, 1.35 x 109 CFU/d of L. fermentum*, 4.05 x 109 CFU/d of B. lactis*, 1.35 x 109 CFU/d of B. breve*, 0.45 x 109 CFU/d of B. bifidum*, and 2.2 x 109 CFU/d of S. thermophilus*	4 weeks + 3 weeks washout	Small reduction in symptoms of GI discomfort compared to placebo	A small-to-moderate reduction in urine lactulose:rhamnose. Significantly lower plasma LPS/GI permeability in probiotic group. No significant difference with IL-6, IL-10, and IL-1ra compared to placebo. No significant differences with hematological variables or urinary claudin-3 pre- vs. post- exercise.	Significant increase in running time to fatigue in high temperatures compared to placebo
O'Brien et al. (68)	67 recreational but untrained subjects; 18–35 years	PC, PPI	Fermented kefir beverage containing undefined Lactobacillus+1 x 109CFU/serving, 2 servings/ week	15 weeks	NR	Plasma c-reactive protein (CRP) increased due to exercise, but no difference due to probiotic intervention.	No performance comparison made with respect to probiotic.
Gill et al. (69)	8 male trained adults; 26 ± 6 years	B, RCT, PC, cross-over	L. casei* (1 × 1011 CFU/d)	1 weeks	NR	No significant changes in resting circulatory endotoxin concentration or plasma cytokine profile compared to placebo. Relative to pre-EHS concentrations, higher plasma concentrations of endotoxin TNF-α were observed compared to placebo.	No performance comparisons were made due to probiotic intervention.
Gleeson et al. (70)	156 male, 112 female recreational athletes; 21 ± 3 years	DB, PC, RCT, parallel	Fermented milk containing L. casei Shirota 6.5 x 109 CFU/2 times per day	16 weeks	No differences related to URS, number of episodes, total symptom score, or episode duration.	Decreased IgG-specific antibodies for cytomegalovirus (CMV) and Epstein-Barr virus compared with baseline of probiotic group. No differences in immune cell counts.	No performance comparisons were made due to probiotic intervention
Michalickova et al. (71)	36 male, 14 female elite athletes; 18–28 years	DB, PC, RCT	Capsules containing L. helveticus LaftiL10 2 x 1010 CFU/d	14 weeks	Decrease in URTI episode duration and number of symptoms compared to placebo. No difference in symptom severity and incidence of URTI between groups.	No significant changes in leukocyte abundance, TBF-β serum levels, IL-10 from peripheral blood mononuclear cells (PBMCs), IFN-γ level from PBMCs or viability/proliferation of PBMCs upon antigen stimulation. Group effect for CD4+/CD8+ ratio was significant.	No performance comparisons were made due to probiotic intervention
Roberts et al. (72)	25 male, 5 female recreational triathletes; 35 ± 1 years	DB, PC, RCT	Capsule containing L. acidophilus (1 x 1010 CFU/d, L. acidophilus CUL-60 [NCIMB 30157] and 1 x 1010 CFU/d L. acidophillus CUL-21 [NCIMB 30156]), 16.8 mg/day B. bifidum and lactis (9.5 x 109 CFU/d B. bifidum CUL-20 [NCIMB30172] and 5 x 108 CFU/d B. animalis subsp. lactis CUL-34 [NCIMB 30153] + 55.8 mg/d fructooligosaccharide (FOS) with or without antixodants	12 weeks	GI symptom episodes were lower in the probiotic + FOS group at each month of prerace training, and the severity of GI symptoms was lower	Reduction in plasma endotoxin levels at pre-race and 6 days post-race, as well as for IgG levels recorded 6 d postrace. No significant difference in GI permeability between groups Lactose:Mannitol increased marginally from baseline to pre-race and 6 days post-race with probiotic +antioxidant.	Non-significant trend of faster overall time to finish in probiotic groups.
Strasser et al. (73)	13 male, 16 female trained athletes; 22–30 years	DB, PC, RCT, parallel	Sachet containing 1 x 1010 CFU multispecies B. bifidum W23 + B. lactisW51 + E. faeciumW54 + L. acidophilusW22 + L. brevis W63 + L. lactisW58	3 months	Incidence of URTI decreased for both groups over 12 weeks, yet fewer probiotic treated subjects had URTI after 12 weeks (5 vs 8).	After the acute exercise, probiotic group lost less tryptophan vs. placebo. Female participants had higher degradation of tryptophan compared with male participants.	Significant increase in training hours per week and decreased resting energy expenditure compared to placebo.
Marshall et al. (38)	24 male, 6 female trained endurance athletes; 23–53 years	RIM, parallel	Capsules with or without glutamine contained 1 x 1010 CFU/d, L. acidophilus CUL-60 and 1 x 1010 CFU/d L. acidophillus CUL-21 16.8 mg/d B. bifidum* and lactis (9.5 x 1010 CFU/d, B. bifidum and 0.5 x 1010 CFU/d B. animalis subspecies lactis, and 55.8 mg/d fructooligosaccharides (FOS)	12 weeks	NR	Blood eHSP72 was not different between nutritional groups (probiotic with or without glutamine).	Time to race completion was not different between groups.
Michalickova et al. (74)	22 male elite athletes; 20–24 years	DB, PC, RCT, parallel	Capsules containing L. helveticus Lafti L10 (2 x 1010 CFU/d)	14 weeks	NR	Decreased malondialdehyde (MDA), superoxide dismutase activity (SOD) serum paraoxonase (PON1) compared to placebo.	No performance comparisons were made due to probiotic administration.
Carbuhn et al. (33)	20 female elite swimmers; 19–23 years	DB, PC, RCT, parallel	Capsules containing B. longum 35624 1 x 109 CFU/d	6 weeks	Mild improvement in RESTQ52-sport weekly self-regulation scores of stress. No URTI or URS measures.	No difference in panel of systemic inflammatory markers. Endotoxin (LPS) and LPS-binding protein (LPB) were not statistically different between groups. Small but significant decrease in the systemic cytokine marker IL-1ra within the probiotic group at mid-training found.	No significant difference between supplemented groups
Komano et al. (75)	51 male recreational athletes; 19–21 years	DB, PC, RCT, parallel	Capsules containing heat killed Lactococcus lactis JCM 5805 1 x 1011 CFU/d	13 days	Significant decrease in some respiratory symptoms and cumulative days of URTI, decreased fatigue accumulation compared to placebo.	CD86 as maturation marker on dendritic cell activity was significantly increased in the probiotic group at day 14.	No difference between training time between groups. No performance comparisons were made due to probiotic intervention.

Updated and adapted from AR 40-501 (2), Davies et al. (27), Pyne et al. (28), Coqueiro et al. (29). B, blinded; CFU, colony forming units; DB, double-blind; eHSP, extracellular heat shock protein; EHS, exertional heat stress GI, gastrointestinal; NR, not reported; PC, placebo controlled, PPI, pre-post intervention; RCT, random controlled trial; RIM, randomized independent measures; TGF, transforming growth factor; URS, upper respiratory symptoms; URTI, upper respiratory tract infections, URI, upper respiratory infection.

^aMean ± SD; and/or range.

^*Strain not reported.

⁺Species/strain not reported.

B., Bifidobacterium; C., Clostridium; E., Enterococcus; L., Lactobacillus, S., Streptococcus.